INDUCTION OF ABUNDANT OSTEOCLAST-LIKE MULTINUCLEATED GIANT-CELLS IN ADJUVANT ARTHRITIC RATS WITH ACCOMPANYING DISORDERED HIGH BONE TURNOVER

The development of an in vivo system for investigating osteoclast diff erentiation is important because molecular events occurring in vivo ca n be observed during the differentiation of the authentic osteoclasts. In adjuvant arthritic rats, an experimental model of human rheumatoid arthritis, extensive bone resorption is observed in the distal diaphy sis of the tibia. In the area of extensive bone resorption, it is alwa ys accompanied with clusters of numerous multinucleated giant cells (M GCs) as well as bone-resorbing osteoclasts. Here we characterized the morphological properties of these MGCs with the use of enzyme-histoche mical and immunohistochemical techniques. Extensive destruction but al so a marked formation of the inner and outer bone surfaces were the pr edominant features in the tibiae of such arthritic rats 4 weeks after the adjuvant injection. Numerous MGCs were frequently clustered in the bone marrow spaces located apart from the bone matrices. Although the MGCs lacked ruffled borders, these cells were rich in mitochondria an d vacuoles. These multinucleated cells revealed a positive reaction fo r tartrate-resistant acid phosphatase but a negative reaction for non- specific esterase staining. Most of these MGCs expressed the Kat 1-ant igen, an immunological marker specifically expressed on the cell surfa ce of rat osteoclasts. In a dentin resorption experiment using a clust er of MGCs excised from the bone marrow tissues of the tibial distal d iaphyses of rats with adjuvant arthritis, many resorption lacunae were formed on dentin slices after a S-day culture. These results suggest that the majority of the MGCs are osteoclasts but not macrophage polyk aryons.